Displaying publications 41 - 60 of 501 in total

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  1. Wan Abdul Rahman WF, Fauzi MH, Jaafar H
    Asian Pac. J. Cancer Prev., 2014;15(19):8441-5.
    PMID: 25339043
    BACKGROUND: Paired-like homeodomain transcription factor 2 (PITX2) is another new marker in breast carcinoma since hypermethylation at P2 promoter of this gene was noted to be associated with poor prognosis. We investigated the expression of PITX2 protein using immunohistochemistry in invasive ductal carcinoma and its association with the established growth receptors such as estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth receptor 2 (HER2).

    METHODS: We conducted a cross sectional study using 100 samples of archived formalin-fixed paraffin embedded tissue blocks of invasive ductal carcinoma and stained them with immunohistochemistry for PITX2, ER, PR and HER2. All HER2 with scoring of 2+ were confirmed with chromogenic in-situ hybridization (CISH).

    RESULTS: PITX2 protein was expressed in 53% of invasive ductal carcinoma and lack of PITX2 expression in 47%. Univariate analysis revealed a significant association between PITX2 expression with PR (p=0.001), ER (p=0.006), gland formation (p=0.044) and marginal association with molecular subtypes of breast carcinoma (p=0.051). Combined ER and PR expression with PITX2 was also significantly associated (p=0.003) especially in double positive cases. Multivariate analysis showed the most significant association between PITX2 and PR (RR 4.105, 95% CI 1.765-9.547, p=0.001).

    CONCLUSION: PITX2 is another potential prognostic marker in breast carcinoma adding significant information to established prognostic factors of ER and PR. The expression of PITX2 together with PR may carry a very good prognosis.

  2. Woodward M
    Asian Pac. J. Cancer Prev., 2014;15(19):8521-6.
    PMID: 25339057
    In many countries of the Association of Southeast Asian Nations (ASEAN), cancer is an increasing problem due to ageing and a transition to Western lifestyles. Governments have been slow to react to the health consequences of these socioeconomic changes, leading to the risk of a cancer epidemic overwhelming the region. A major limitation to motivating change is the paucity of high-quality data on cancer, and its socioeconomic repercussions, in ASEAN. Two initiatives have been launched to address these issues. First, a study of over 9000 new cancer patients in ASEAN - the ACTION study - which records information on financial difficulties, as well as clinical outcomes, subsequent to the diagnosis. Second, a series of roundtable meetings of key stakeholders and experts, with the broad aim of producing advice for governments in ASEAN to take appropriate account of issues relating to cancer, as well as to generate knowledge and interest through engagement with the media. An important product of these roundtables has been the Jakarta Call to Action on Cancer Control. The growth and ageing of populations is a global challenge for cancer services. In the less developed parts of Asia, and elsewhere, these problems are compounded by the epidemiological transition to Western lifestyles and lack of awareness of cancer at the government level. For many years, health services in less developed countries have concentrated on infectious diseases and mother-and-child health; despite a recent wake-up call (United Nations, 2010), these health services have so far failed to allow for the huge increase in cancer cases to come. It has been estimated that, in Asia, the number of new cancer cases per year will grow from 6.1 million in 2008 to 10.6 million in 2030 (Sankaranarayanan et al., 2014). In the countries of the Association of Southeast Asian Nations (ASEAN), corresponding figures are 770 thousand in 2012 (Figure 1), rising to 1.3 million in 2030 (Ferlay et al., 2012). ASEAN consists of Brunei Darussalam, Cambodia, Indonesia, Lao, Malaysia, Myanmar, the Philippines, Singapore, Thailand and Viet Nam. It, thus, includes low- and middle-income countries where the double whammy of infectious and chronic diseases will pose an enormous challenge in allocating limited resources to competing health issues. Cancer statistics, even at the sub-national level, only tell part of the story. Many individuals who contract cancer in poor countries have no medical insurance and no, or limited, expectation of public assistance. Whilst any person who has a family member with cancer can expect to bear some consequential burden of care or expense, in a poor family in a poor environment the burden will surely be greater. This additional burden from cancer is rarely considered, and even more rarely quantified, even in developed nations.
  3. Zamaniah WI, Mastura MY, Phua CE, Adlinda A, Marniza S, Rozita AM
    Asian Pac. J. Cancer Prev., 2014;15(20):8987-92.
    PMID: 25374241
    BACKGROUND: The efficacy of concurrent chemoradiotherapy in the treatment of locally advanced cervical cancer is well established. We aimed to investigate the long-term efficacy of definitive concurrent chemoradiotherapy for cervical cancer in the University of Malaya Medical Centre.

    MATERIALS AND METHODS: A cohort of 60 patients with FIGO stage IB2-IVA cervical cancer who were treated with definitive concurrent chemoradiotherapy with cisplatin followed by intracavitary brachytherapy or external beam radiotherapy (EBRT) boost between November 2001 and May 2008 were analysed. Patients were initially treated with weekly intravenous cisplatin (40 mg/m2) concurrent with daily EBRT to pelvis of 45-50 Gy followed by low dose rate brachytherapy or EBRT boost to tumour. Local control rate, progression free survival, overall survival and treatment related toxicities graded by the RTOG criteria were evaluated.

    RESULTS: The mean age was 56. At the median follow-up of 72 months, the estimated 5-year progression-free survival (PFS) (median PFS 39 months) and the 5-year overall survival (OS) (median OS 51 months) were 48% and 50% respectively. The 5-year local control rate was 67.3%. Grade 3-4 late gastrointestinal and genitourinary toxicity occurred in 9.3% of patients.

    CONCLUSIONS: The 5-year PFS and the 5-year OS in this cohort were lower than in other institutions. More advanced stage at presentation, longer overall treatment time (OTT) of more than fifty-six days and lower total dose to point A were the potential factors contributing to a lower survival.

  4. Khor GH, Froemming GR, Zain RB, Abraham MT, Thong KL
    Asian Pac. J. Cancer Prev., 2014;15(20):8957-61.
    PMID: 25374236
    BACKGROUND: Promoter hypermethylation leads to altered gene functions and may result in malignant cellular transformation. Thus, identification of biomarkers for hypermethylated genes could be useful for diagnosis, prognosis, and therapeutic treatment of oral squamous cell carcinoma (OSCC).

    OBJECTIVES: To screen hypermethylated genes with a microarray approach and to validate selected hypermethylated genes with the methylation-specific polymerase chain reaction (MSPCR).

    MATERIALS AND METHODS: Genome-wide analysis of normal oral mucosa and OSCC tissues was conducted using the Illumina methylation microarray. The specified differential genes were selected and hypermethylation status was further verified with an independent cohort sample of OSCC samples. Candidate genes were screened using microarray assay and run by MSPCR analysis.

    RESULTS: TP73, PIK3R5, and CELSR3 demonstrated high percentages of differential hypermethylation status.

    CONCLUSIONS: Our microarray screening and MSPCR approaches revealed that the signature candidates of differentially hypermethylated genes may possibly become potential biomarkers which would be useful for diagnostic, prognostic and therapeutic targets of OSCC in the near future.

  5. Amtha R, Razak IA, Basuki B, Roeslan BO, Gautama W, Puwanto DJ, et al.
    Asian Pac. J. Cancer Prev., 2014;15(20):8673-8.
    PMID: 25374188
    PURPOSE: This study aimed to determine the association between tobacco consumption (kretek) and betel quid chewing with oral cancer risk.

    MATERIALS AND METHODS: A total of 81 cases of oral cancers were matched with 162 controls in this hospital-based study. Information on sociodemographic characteristics and details of risk habits (duration, frequency and type of tobacco consumption and betel quid chewing) were collected. Association between smoking and betel quid chewing with oral cancer were analysed using conditional logistic regression.

    RESULTS: Slightly more than half of the cases (55.6%) were smokers where 88.9% of them smoked kretek. After adjusting for confounders, smokers have two fold increased risk, while the risk for kretek consumers and those smoking for more than 10 years was increased to almost three-fold. Prevalence of betel quid chewing among cases and controls was low (7.4% and 1.9% respectively). Chewing of at least one quid per day, and quid combination of betel leaf, areca nut, lime and tobacco conferred a 5-6 fold increased risk.

    CONCLUSIONS: Smoking is positively associated with oral cancer risk. A similar direct association was also seen among betel quid chewers.

  6. Abdull Razis AF, Ibrahim MD, Kntayya SB
    Asian Pac. J. Cancer Prev., 2014;15(20):8571-6.
    PMID: 25374169
    Phytomedicines are believed to have benefits over conventional drugs and are regaining interest in current research. Moringa oleifera is a multi-purpose herbal plant used as human food and an alternative for medicinal purposes worldwide. It has been identified by researchers as a plant with numerous health benefits including nutritional and medicinal advantages. Moringa oleifera contains essential amino acids, carotenoids in leaves, and components with nutraceutical properties, supporting the idea of using this plant as a nutritional supplement or constituent in food preparation. Some nutritional evaluation has been carried out in leaves and stem. An important factor that accounts for the medicinal uses of Moringa oleifera is its very wide range of vital antioxidants, antibiotics and nutrients including vitamins and minerals. Almost all parts from Moringa can be used as a source for nutrition with other useful values. This mini-review elaborate on details its health benefits.
  7. Othman NH, Mohamad Zaki FH
    Asian Pac. J. Cancer Prev., 2014;15(20):8563-9.
    PMID: 25374168
    Sub-optimal participation is a major problem with cervical cancer screening in developing countries which have no organized national screening program. There are various notable factors such as 'embarrassment', 'discomfort' and 'no time' cited by women as they are often also the bread winners for the family. Implementation of self-sampling methods may increase their participation. The aim of this article was to provide a survey of various types of self-sampling tools which are commonly used in collection of cervical cells. We reviewed currently available self-sampling devices and collated the advantages and disadvantages of each in terms of its acceptance and its accuracy in giving desired results. In general, regardless of which device is used, self-sampling for cervical scrapings is highly acceptable to women in most of the studies cited.
  8. Tengku Din TA, Seeni A, Khairi WN, Shamsuddin S, Jaafar H
    Asian Pac. J. Cancer Prev., 2014;15(24):10659-63.
    PMID: 25605156
    BACKGROUND: Rapamycin is an effective anti-angiogenic drug. However, the mode of its action remains unclear. Therefore, in this study, we aimed to elucidate the antitumor mechanism of rapamycin, hypothetically via apoptotic promotion, using MCF-7 breast cancer cells.

    MATERIALS AND METHODS: MCF-7 cells were plated at a density of 15105 cells/well in 6-well plates. After 24h, cells were treated with a series of concentrations of rapamycin while only adding DMEM medium with PEG for the control regiment and grown at 37oC, 5% CO2 and 95% air for 72h. Trypan blue was used to determine the cell viability and proliferation. Untreated and rapamycin-treated MCF-7 cells were also examined for morphological changes with an inverted-phase contrast microscope. Alteration in cell morphology was ascertained, along with a stage in the cell cycle and proliferation. In addition, cytotoxicity testing was performed using normal mouse breast mammary pads.

    RESULTS: Our results clearly showed that rapamycin exhibited inhibitory activity on MCF-7 cell lines. The IC50 value of rapamycin on the MCF-7 cells was determined as 0.4μg/ml (p<0.05). Direct observation by inverted microscopy demonstrated that the MCF-7 cells treated with rapamycin showed characteristic features of apoptosis including cell shrinkage, vascularization and autophagy. Cells underwent early apoptosis up to 24% after 72h. Analysis of the cell cycle showed an increase in the G0G1 phase cell population and a corresponding decrease in the S and G2M phase populations, from 81.5% to 91.3% and 17.3% to 7.9%, respectively.

    CONCLUSIONS: This study demonstrated that rapamycin may potentially act as an anti-cancer agent via the inhibition of growth with some morphological changes of the MCF-7 cancer cells, arrest cell cycle progression at G0/G1 phase and induction of apoptosis in late stage of apoptosis. Further studies are needed to further characterize the mode of action of rapamycin as an anti-cancer agent.

  9. Al-Naggar RA, Bobryshev YV, Anil S
    Asian Pac. J. Cancer Prev., 2014;15(24):10841-6.
    PMID: 25605187
    BACKGROUND: Smoking is a primary risk factor for cancer development. While most research has focused on smoking cigarettes, the increasing popularity of shisha or water pipe smoking has received less attention. This study measured the prevalence and risk factors for shisha and cigarette smoking and related knowledge.

    MATERIALS AND METHODS: This cross-sectional analytical study was conducted in Shah Alam, Malaysia. Participants aged ≥ 18 years were selected from restaurants. Data regarding demographic variables, smoking patterns, and knowledge about shisha smoking were collected in local languages. Logistic regression was performed to assess risk factors.

    RESULTS: Of 239 participants, 61.9 % were male and 99.2% revealed their smoking status. Some 57.4% were smokers: 50.7% only cigarettes, 5.9% only shisha and 42% both. Mean age of starting cigarette smoking was 17.5 ± 2.4 years and for shisha smoking 18.7 ± 2.0 years. In a univariate model, male gender, age 33-52 years and monthly income > MYR 4,000 increased the risk and unemployment and being a student decreased the risk. In a multivariate model, male gender increased the risk of smoking, while being a student decreased the risk, adjusting for age and income. The perception of shisha being less harmful than cigarettes was present in 14.6% and 7.5% had the opinion that shisha is not harmful at all, while 21.7% said that it is less addictive than cigarettes, 39.7% said that shisha did not contain tar and nicotine, 34.3% said that it did not contain carbon monoxide and 24.3% thought that shisha did not cause health problems.

    CONCLUSIONS: Prevalence of shisha and cigarette smoking is high in the general population in Malaysia and knowledge about shisha smoking is relatively low. The findings of our study might have implications for understanding similarities and differences in incidence of shisha and cigarette smoking in other cultural/geographic regions.

  10. Kavitha N, Vijayarathna S, Jothy SL, Oon CE, Chen Y, Kanwar JR, et al.
    Asian Pac. J. Cancer Prev., 2014;15(18):7489-97.
    PMID: 25292018
    MicroRNAs (miRNAs) are short non-coding RNAs of 20-24 nucleotides that play important roles in carcinogenesis. Accordingly, miRNAs control numerous cancer-relevant biological events such as cell proliferation, cell cycle control, metabolism and apoptosis. In this review, we summarize the current knowledge and concepts concerning the biogenesis of miRNAs, miRNA roles in cancer and their potential as biomarkers for cancer diagnosis and prognosis including the regulation of key cancer-related pathways, such as cell cycle control and miRNA dysregulation. Moreover, microRNA molecules are already receiving the attention of world researchers as therapeutic targets and agents. Therefore, in-depth knowledge of microRNAs has the potential not only to identify their roles in cancer, but also to exploit them as potential biomarkers for cancer diagnosis and identify therapeutic targets for new drug discovery.
  11. Rashid RM, Ramli S, John J, Dahlui M
    Asian Pac. J. Cancer Prev., 2014;15(13):5143-7.
    PMID: 25040965
    Cervical cancer screening in Malaysia is by opportunistic Pap smear which contributes to the low uptake rate. To overcome this, a pilot project called the SIPPS program (translated as information system of Pap smear program) had been introduced whereby women aged 20-65 years old are invited for Pap smear and receive recall to repeat the test. This study aimed at determining which recall method is most cost-effective in getting women to repeat Pap smear. A randomised control trial was conducted where one thousand women were recalled for repeat smear either by registered letter, phone messages, phone call or the usual postal letter. The total cost applied for cost-effectiveness analysis includes the cost of sending letter for first invitation, cost of the recall method and cost of two Pap smears. Cost-effective analysis (CEA) of Pap smear uptake by each recall method was then performed. The uptake of Pap smear by postal letter, registered letters, SMS and phone calls were 18.8%, 20.0%, 21.6% and 34.4%, respectively (p<0.05). The CER for the recall method was lowest by phone call compared to other interventions; RM 69.18 (SD RM 0.14) compared to RM 106.53 (SD RM 0.13), RM 134.02 (SD RM 0.15) and RM 136.38 (SD RM 0.11) for SMS, registered letter and letter, respectively. ICER showed that it is most cost saving if the usual method of recall by postal letter be changed to recall by phone call. The possibility of letter as a recall for repeat Pap smear to reach the women is higher compared to sending SMS or making phone call. However, getting women to do repeat Pap smear is better with phone call which allows direct communication. Despite the high cost of the phone call as a recall method for repeat Pap smear, it is the most cost-effective method compared to others.
  12. Chan HK, Ismail S
    Asian Pac. J. Cancer Prev., 2014;15(13):5305-9.
    PMID: 25040993
    BACKGROUND: This study aimed to assess the most common physical side effects experienced by local chemotherapy patients. Their perceptions of these side effects and informational needs from clinical pharmacists were also evaluated.

    MATERIALS AND METHODS: This was a single-center, cross-sectional study. A face-to-face interview guided by a structured questionnaire with cancer patients admitted to receive repeated cycles of chemotherapy was conducted. Information collected included chemotherapy-related side effects after last chemotherapy experience, the most worrisome side effects, the side effects overlooked by healthcare professionals and the preferred method, amount and source of receiving related information.

    RESULTS: Of 99 patients recruited, 90 participated in this survey (response rate: 90.9%). The majority were in the age range of 45-64 years (73.3%) and female (93.3%). Seventy-five (83.3%) and seventy-one (78.9%) experienced nausea and vomiting, respectively. Both symptoms were selected as two of the most worrisome side effects (16.7% vs. 33.3%). Other common and worrisome side effects were hair loss and loss of appetite. Symptoms caused by peripheral neuropathies were perceived as the major symptoms being overlooked (6.7%). Most patients demanded information about side effects (60.0%) and they would like to receive as much information as possible (86.7%). Oral conversation (83.3%) remained as the preferred method and the clinical pharmacist was preferred by 46.7% of patients as the educator in this aspect.

    CONCLUSIONS: The high prevalence of chemotherapy-related side effects among local patients is of concern. Findings of their perceptions and informational needs may serve as a valuable guide for clinical pharmacists to help in side effect management in Malaysia.

  13. Azmawati MN, Najibah E, Hatta MD, Norfazilah A
    Asian Pac. J. Cancer Prev., 2014;15(13):5283-6.
    PMID: 25040989
    Stage of cervical cancer may adversely affect the quality of life (QOL) among patients. The objective of this study was to predict the QOL among cervical cancer patients by the stage of their cancer. A cross-sectional study from September 2012 until January 2013 was conducted among cervical cancer patients who completed treatment. All patients completed a interviewer-guided questionnaire comprising four sections: (A) socio- demographic data, (B) medical history, (C) QOL measured by general health status questionnaire (QLQ-30) and (D) cervical cancer specific module CX-24 (EORTC) was used to measured patient's functional, symptom scale and their global health status. Results showed that global health status, emotional functioning and pain score were higher in stage III cervical cancer patients while role functioning was higher in stage I cervical cancer patients. Patients with stage IV cancer have a lower mean score in global health status (adjusted b-22.0, 95 CI% -35.6, -8.49) and emotional functioning (adjusted b -22.5, 95 CI% -38.1, -6.69) while stage III had lower mean score in role functioning (adjusted b -14.3, 95 CI% -25.4, -3.21) but higher mean score in pain (adjusted b 22.1, 95 CI% 8.56, 35.7). In conclusion, stage III and IV cervical cancers mainly affect the QOL of cervical cancer patients. Focus should be given to these subgroups to help in improving the QOL.
  14. Hashim N, Jamalludin Z, Ung NM, Ho GF, Malik RA, Phua VC
    Asian Pac. J. Cancer Prev., 2014;15(13):5259-64.
    PMID: 25040985
    BACKGROUND: CT based brachytherapy allows 3-dimensional (3D) assessment of organs at risk (OAR) doses with dose volume histograms (DVHs). The purpose of this study was to compare computed tomography (CT) based volumetric calculations and International Commission on Radiation Units and Measurements (ICRU) reference-point estimates of radiation doses to the bladder and rectum in patients with carcinoma of the cervix treated with high-dose-rate (HDR) intracavitary brachytherapy (ICBT).

    MATERIALS AND METHODS: Between March 2011 and May 2012, 20 patients were treated with 55 fractions of brachytherapy using tandem and ovoids and underwent post-implant CT scans. The external beam radiotherapy (EBRT) dose was 48.6 Gy in 27 fractions. HDR brachytherapy was delivered to a dose of 21 Gy in three fractions. The ICRU bladder and rectum point doses along with 4 additional rectal points were recorded. The maximum dose (DMax) to rectum was the highest recorded dose at one of these five points. Using the HDR plus 2.6 brachytherapy treatment planning system, the bladder and rectum were retrospectively contoured on the 55 CT datasets. The DVHs for rectum and bladder were calculated and the minimum doses to the highest irradiated 2cc area of rectum and bladder were recorded (D2cc) for all individual fractions. The mean D2cc of rectum was compared to the means of ICRU rectal point and rectal DMax using the Student's t-test. The mean D2cc of bladder was compared with the mean ICRU bladder point using the same statistical test .The total dose, combining EBRT and HDR brachytherapy, were biologically normalized to the conventional 2 Gy/fraction using the linear-quadratic model. (α/β value of 10 Gy for target, 3 Gy for organs at risk).

    RESULTS: The total prescribed dose was 77.5 Gy α/β10. The mean dose to the rectum was 4.58 ± 1.22 Gy for D 2cc, 3.76 ± 0.65 Gy at D ICRU and 4.75 ± 1.01 Gy at DMax. The mean rectal D 2cc dose differed significantly from the mean dose calculated at the ICRU reference point (p<0.005); the mean difference was 0.82 Gy (0.48 -1.19 Gy). The mean EQD2 was 68.52 ± 7.24 Gy α/β3 for D 2cc, 61.71 ± 2.77 Gy α/β3 at D ICRU and 69.24 ± 6.02 Gy α/β3 at DMax. The mean ratio of D 2cc rectum to D ICRU rectum was 1.25 and the mean ratio of D 2cc rectum to DMax rectum was 0.98 for all individual fractions. The mean dose to the bladder was 6.00 ± 1.90 Gy for D 2cc and 5.10 ± 2.03 Gy at D ICRU. However, the mean D 2cc dose did not differ significantly from the mean dose calculated at the ICRU reference point (p=0.307); the mean difference was 0.90 Gy (0.49-1.25 Gy). The mean EQD2 was 81.85 ± 13.03 Gy α/β3 for D 2cc and 74.11 ± 19.39 Gy α/β3 at D ICRU. The mean ratio of D 2cc bladder to D ICRU bladder was 1.24. In the majority of applications, the maximum dose point was not the ICRU point. On average, the rectum received 77% and bladder received 92% of the prescribed dose.

    CONCLUSIONS: OARs doses assessed by DVH criteria were higher than ICRU point doses. Our data suggest that the estimated dose to the ICRU bladder point may be a reasonable surrogate for the D 2cc and rectal DMax for D 2cc. However, the dose to the ICRU rectal point does not appear to be a reasonable surrogate for the D 2cc.

  15. Osman HA, Hasan H, Suppian R, Bahar N, Hussin NS, Rahim AA, et al.
    Asian Pac. J. Cancer Prev., 2014;15(13):5245-7.
    PMID: 25040982
    BACKGROUND: Helicobacter pylori (H. pylori) is one of the most important causes of dyspepsia and gastric cancer and diagnosis can be made by invasive or non-invasive methods. The Atlas Helicobacter pylori antigen test is a new rapid non-invasive method which is simple to conduct. The aim of this study was to determine its sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy.

    MATERIALS AND METHODS: This prospective study was conducted between July 2012 and December 2013. Stool samples of 59 dyspeptic patients who underwent upper endoscopy were evaluated for H. pylori stool antigen.

    RESULTS: From the 59 patients who participated in this study, there were 36 (61%) males and 23 (39%) females. H. pylori was diagnosed in 24 (40.7%) gastric biopsies, 22 (91.7 %) of these being positive for the Atlas H. pylori antigen test. The sensitivity, specificity, PPV, NPV and accuracy were 91.7%, 100%, 100%, 94.6% and 96.6% respectively.

    CONCLUSIONS: The Atlas H. pylori antigen test is a new non-invasive method which is simple to perform and avails reliable results in a few minutes. Thus it can be the best option for the diagnosis of H. pylori infection due to its high sensitivity and specificity.

  16. Al-Jamal HA, Jusoh SA, Yong AC, Asan JM, Hassan R, Johan MF
    Asian Pac. J. Cancer Prev., 2014;15(11):4555-61.
    PMID: 24969884
    BACKGROUND: Silencing due to methylation of suppressor of cytokine signaling-3 (SOCS-3), a negative regulator gene for the JAK/STAT signaling pathway has been reported to play important roles in leukemogenesis. Imatinib mesylate is a tyrosine kinase inhibitor that specifically targets the BCR-ABL protein and induces hematological remission in patients with chronic myeloid leukemia (CML). Unfortunately, the majority of CML patients treated with imatinib develop resistance under prolonged therapy. We here investigated the methylation profile of SOCS-3 gene and its downstream effects in a BCR-ABL positive CML cells resistant to imatinib.

    MATERIALS AND METHODS: BCR-ABL positive CML cells resistant to imatinib (K562-R) were developed by overexposure of K562 cell lines to the drug. Cytotoxicity was determined by MTS assays and IC50 values calculated. Apoptosis assays were performed using annexin V-FITC binding assays and analyzed by flow cytometry. Methylation profiles were investigated using methylation specific PCR and sequencing analysis of SOCS-1 and SOCS-3 genes. Gene expression was assessed by quantitative real-time PCR, and protein expression and phosphorylation of STAT1, 2 and 3 were examined by Western blotting.

    RESULTS: The IC50 for imatinib on K562 was 362 nM compared to 3,952 nM for K562-R (p=0.001). Percentage of apoptotic cells in K562 increased upto 50% by increasing the concentration of imatinib, in contrast to only 20% in K562-R (p<0.001). A change from non-methylation of the SOCS-3 gene in K562 to complete methylation in K562-R was observed. Gene expression revealed down- regulation of both SOCS-1 and SOCS-3 genes in resistant cells. STAT3 was phosphorylated in K562-R but not K562.

    CONCLUSIONS: Development of cells resistant to imatinib is feasible by overexposure of the drug to the cells. Activation of STAT3 protein leads to uncontrolled cell proliferation in imatinib resistant BCR-ABL due to DNA methylation of the SOCS-3 gene. Thus SOCS-3 provides a suitable candidate for mechanisms underlying the development of imatinib resistant in CML patients.

  17. Haris K, Ismail S, Idris Z, Abdullah JM, Yusoff AA
    Asian Pac. J. Cancer Prev., 2014;15(11):4499-505.
    PMID: 24969876
    Glioblastoma, the most aggressive and malignant form of glioma, appears to be resistant to various chemotherapeutic agents. Hence, approaches have been intensively investigated to targeti specific molecular pathways involved in glioblastoma development and progression. Aloe emodin is believed to modulate the expression of several genes in cancer cells. We aimed to understand the molecular mechanisms underlying the therapeutic effect of Aloe emodin on gene expression profiles in the human U87 glioblastoma cell line utilizing microarray technology. The gene expression analysis revealed that a total of 8,226 gene alterations out of 28,869 genes were detected after treatment with 58.6 μg/ml for 24 hours. Out of this total, 34 genes demonstrated statistically significant change (p<0.05) ranging from 1.07 to 1.87 fold. The results revealed that 22 genes were up-regulated and 12 genes were down-regulated in response to Aloe emodin treatment. These genes were then grouped into several clusters based on their biological functions, revealing induction of expression of genes involved in apoptosis (programmed cell death) and tissue remodelling in U87 cells (p<0.01). Several genes with significant changes of the expression level e.g. SHARPIN, BCAP31, FIS1, RAC1 and TGM2 from the apoptotic cluster were confirmed by quantitative real-time PCR (qRT-PCR). These results could serve as guidance for further studies in order to discover molecular targets for the cancer therapy based on Aloe emodin treatment.
  18. Hakim L, Alias E, Makpol S, Ngah WZ, Morad NA, Yusof YA
    Asian Pac. J. Cancer Prev., 2014;15(11):4651-7.
    PMID: 24969899
    The development of chemopreventive approaches using a concoction of phytochemicals is potentially viable for combating many types of cancer including colon carcinogenesis. This study evaluated the anti-proliferative effects of ginger and Gelam honey and its efficacy in enhancing the anti-cancer effects of 5-FU (5-fluorouracil) against a colorectal cancer cell line, HCT 116. Cell viability was measured via MTS (3-(4,5-dimethylthiazol-2- yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulphenyl)-2H-tetrazolium) assay showing ginger inhibiting the growth of HCT 116 cells more potently (IC50 of 3mg/mL) in comparison to Gelam honey (IC50 of 75 mg/mL). Combined treatment of the two compounds (3mg/mL ginger+75 mg/mL Gelam honey) synergistically lowered the IC50 of Gelam honey to 22 mg/mL. Combination with 35 mg/mL Gelam honey markedly enhanced 5-FU inhibiting effects on the growth of HCT 116 cells. Subsequent analysis on the induction of cellular apoptosis suggested that individual treatment of ginger and Gelam honey produced higher apoptosis than 5-FU alone. In addition, treatment with the combination of two natural compounds increased the apoptotic rate of HCT 116 cells dose- dependently while treatment of either ginger or Gelam honey combined with 5-FU only showed modest changes. Combination index analysis showed the combination effect of both natural compounds to be synergistic in their inhibitory action against HCT 116 colon cancer cells (CI 0.96 < 1). In conclusion, combined treatment of Gelam honey and ginger extract could potentially enhance the chemotherapeutic effect of 5-FU against colorectal cancer.
  19. Magaji BA, Moy FM, Roslani AC, Law CW
    Asian Pac. J. Cancer Prev., 2014;15(15):6059-64.
    PMID: 25124558
    BACKGROUND: Colorectal cancer is the second most frequent cancer in Malaysia. Nevertheless, there is little information on treatment and outcomes nationally. We aimed to determine the demographic, clinical and treatment characteristics of colorectal cancer patients treated at the University Malaya Medical Centre (UMMC) as part of a larger project on survival and quality of life outcomes.

    MATERIALS AND METHODS: Medical records of 1,212 patients undergoing treatment in UMMC between January 2001 and December 2010 were reviewed. A retrospective-prospective cohort study design was used. Research tools included the National Cancer Patient Registration form. Statistical analysis included means, standard deviations (SD), proportions, chi square, t-test/ ANOVA. P-value significance was set at 0.05.

    RESULTS: The male: female ratio was 1.2:1. The mean age was 62.1 (SD12.4) years. Patients were predominantly Chinese (67%), then Malays (18%), Indians (13%) and others (2%). Malays were younger than Chinese and Indians (mean age 57 versus 62 versus 62 years, p<0.001). More females (56%) had colon cancers compared to males (44%) (p=0.022). Malays (57%) had more rectal cancer compared to Chinese (45%) and Indians (49%) (p=0.004). Dukes' stage data weres available in 67%, with Dukes' C and D accounting for 64%. Stage was not affected by age, gender, ethnicity or tumor site. Treatment modalities included surgery alone (40%), surgery and chemo/radiotherapy 32%, chemo and radiotherapy (8%) and others (20%).

    CONCLUSIONS: Significant ethnic differences in age and site distribution, if verified in population-based settings, would support implementation of preventive measures targeting those with the greatest need, at the right age.

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